PROK2

What is PROK2 protein?

PROK2 (prokineticin 2) gene is a protein coding gene which situated on the short arm of chromosome 3 at locus 3p13. This gene encodes a protein expressed in the suprachiasmatic nucleus (SCN) circadian clock that may function as the output component of the circadian clock. The secreted form of the encoded protein may also serve as a chemoattractant for neuronal precursor cells in the olfactory bulb. Proteins from other vertebrates which are similar to this gene product were isolated based on homology to snake venom and secretions from frog skin, and have been shown to have diverse functions. The PROK2 protein is consisted of 129 amino acids and its molecular mass is approximately 14.3 kDa.

What is the function of PROK2 protein?

PROK2 is a neuroactive protein that acts primarily as a signaling molecule between glial cells and is involved in regulating the function of the central nervous system. PROK2 has been found to be involved in a variety of physiological processes, including regulation of the reproductive system, neuroprotection, anti-inflammatory response, and angiogenesis. In the reproductive system, PROK2 is involved in regulating the secretion of sex hormones, the development of reproductive organs and ovulation. In the central nervous system, PROK2 is involved in regulating neuronal function, neuroprotection, and the perception of pain.

Fig1. Main effects of prokineticin 2 in the control of metabolism and energy balance. GLUT4: glucose transporter 4. (Christophe Magnan, 2021)

PROK2 Related Signaling Pathway

PROK2 activates its specific G protein-coupled receptors (GPCRs) by binding to its receptor PROKR2. PROK2 can also act as a chemokine, attracting immune cells to the site of inflammation and participating in the regulation of inflammatory response. PROK2 plays a role in angiogenesis, promoting the formation of new blood vessels. In addition, in the sensory nervous system, PROK2 is involved in pain transmission and regulation by acting on PROKR2-positive neurons.

PROK2 Related Diseases

Abnormal function of PROK2 protein can lead to related diseases, including: abnormal function of reproductive system; The hypothalamus function is impaired, which affects various regulatory functions in the body. Diseases related to the nervous system such as schizoid epilepsy in the hospital; Certain diseases associated with pain transmission or inflammation, etc.

Bioapplications of PROK2

Due to its diverse functions, PROK2 and its analogs have been explored as potential therapeutic agents in various conditions, including reproductive disorders, neurological diseases, and vascular disorders. Research is ongoing to investigate the therapeutic potential of targeting PROK2 signaling pathways in different diseases.

Case study 1: Terry C Yin, 2023

Energy homeostasis is a complex system involving multiple hormones, neuropeptides, and receptors. Prokineticins (PK1 and PK2) are agonists to two G protein-coupled receptors, prokineticin receptor 1 and 2 (PKR1 and PKR2), which decrease food intake when injected in rodents. The relative contribution of PKR1 and PKR2 to the anorexigenic effect of PK2 and their site of action in the brain have not yet been elucidated. PKR trafficking and signaling are inhibited by the melanocortin receptor accessory protein 2 (MRAP2), thus suggesting that MRAP2 has the potential to alter the anorexigenic activity of PK2 in vivo.

In this study, the researchers investigated the importance of PKR1 and PKR2 for PK2-mediated inhibition of food intake, the brain region involved in this function, and the effect of MRAP2 on PK2 action in vivo. Using targeted silencing of PKR2 and chemogenetic manipulation of PKR2 neurons, they show that the anorexigenic effect of PK2 is mediated by PKR2 in the amygdala and that altering MRAP2 expression in PKR2 neurons modulates the activity of PK2.

Fig1. PKR1 is not required for PK2-mediated feeding behavior. Food intake after overnight fast and central administration of vehicle (black) or 0.65 μg PK2 (red) in male (n = 18) and female (n = 25) WT

Fig2. MRAP2 expression in PKR2 neurons modulates the anorexigenic activity of PK2. Food intake in overnight fasted male (A) and female (B) PKR2CRE mice injected ICV with vehicle or 0.65 μg PK2.

Case study 2: Kentaro Noda, 2021

Prokineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and circadian rhythms. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, the role of PK2 in the pathogenesis of rheumatoid arthritis (RA) or osteoarthritis (OA) remains unknown.

In this study, the researchers collected synovial tissue, plasma, synovial fluid, and synovial fibroblasts (SF) from RA and OA patients to analyze the function of PK2 using immunohistochemistry, enzyme-linked immunosorbent assays, and tissue superfusion studies. PK2 and its receptors prokineticin receptor (PKR) 1 and 2 were expressed in RA and OA synovial tissues. The PK2 concentration was higher in RA synovial fluid than in OA synovial fluid but similar between RA and OA plasma. PK2 suppressed the production of IL-6 from TNFα-prestimulated OA-SF, and this effect was attenuated in TNFα-prestimulated RA-SF.

Fig3. Immunofluorescent staining of PK2, PKR1, and PKR2 proteins in OA- and RA-SF.

Fig4. Comparison of plasma (N = 20) and synovial fluid (N = 50) PK2 concentrations between OA and RA patients.

PROK2 has several biochemical functions, for example, G-protein coupled receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PROK2 itself. We selected most functions PROK2 had, and list some proteins which have the same functions with PROK2. You can find most of the proteins on our site.

PROK2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PROK2 here. Most of them are supplied by our site. Hope this information will be useful for your research of PROK2.